The B-cell inhibitory receptor CD22 is a major factor in host resistance to Streptococcus pneumoniae infection
Autoři:
Vitor E. Fernandes aff001; Giuseppe Ercoli aff002; Alan Bénard aff003; Carolin Brandl aff004; Hannah Fahnenstiel aff004; Jennifer Müller-Winkler aff004; Georg F. Weber aff003; Paul Denny aff005; Lars Nitschke aff004; Peter W. Andrew aff001
Působiště autorů:
Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom
aff001; Department of Genetics, University of Leicester, Leicester, United Kingdom
aff002; Department of Surgery, University Hospital Erlangen, Erlangen, Germany
aff003; Division of Genetics, Department of Biology, University of Erlangen, Erlangen, Germany
aff004; Mammalian Genetics Unit, Medical Research Council, Harwell, United Kingdom
aff005
Vyšlo v časopise:
The B-cell inhibitory receptor CD22 is a major factor in host resistance to Streptococcus pneumoniae infection. PLoS Pathog 16(4): e32767. doi:10.1371/journal.ppat.1008464
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.ppat.1008464
Souhrn
Streptococcus pneumoniae is a major human pathogen, causing pneumonia and sepsis. Genetic components strongly influence host responses to pneumococcal infections, but the responsible loci are unknown. We have previously identified a locus on mouse chromosome 7 from a susceptible mouse strain, CBA/Ca, to be crucial for pneumococcal infection. Here we identify a responsible gene, Cd22, which carries a point mutation in the CBA/Ca strain, leading to loss of CD22 on B cells. CBA/Ca mice and gene-targeted CD22-deficient mice on a C57BL/6 background are both similarly susceptible to pneumococcal infection, as shown by bacterial replication in the lungs, high bacteremia and early death. After bacterial infections, CD22-deficient mice had strongly reduced B cell populations in the lung, including GM-CSF producing, IgM secreting innate response activator B cells, which are crucial for protection. This study provides striking evidence that CD22 is crucial for protection during invasive pneumococcal disease.
Klíčová slova:
B cells – Blood – Escherichia coli infections – Genetic loci – Pneumococcus – Respiratory infections – Spleen – Streptococcal infections
Zdroje
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